Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment...

BACKGROUND: The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization...

PURPOSE: To explore the use of the frequency of the energy deposition (ED) clusters of different sizes (cluster order, CO) as a surrogate (instead of, e.g., LET) classification of the physical characteristics of ionizing radiation at a nanometer scale, to construct a framework for the calculation of relative biological effectiveness (RBE) with cell survival as endpoint. METHODS: The frequency of cluster order fCO is calculated by sorting the ED sites generated with the Monte Carlo track structure code LIonTrack into clusters based on a single parameter called the cluster distance dC being the maximum allowed distance between two neighboring EDs belonging to a cluster...

BACKGROUND: Early controlled ankle motion is widely used in the non-operative treatment of acute Achilles tendon rupture, though its safety and efficacy have never been investigated in a randomized setup. The objectives of this study are to investigate if early controlled motion of the ankle affects functional and patient-reported outcomes. METHODS/DESIGN: The study is performed as a blinded, randomized, controlled trial with patients allocated in a 1:1 ratio to one of two parallel groups...

BACKGROUND: After the Fukushima Dai-ichi Nuclear Power Station accident in Japan on March 11, 2011, a large number of comments, both positive and negative, were posted on social media. OBJECTIVE: The objective of this study was to clarify the characteristics of the trend in the number of tweets posted on Twitter, and to estimate how long public concern regarding the accident continued. We surveyed the attenuation period of the first term occurrence related to radiation exposure as a surrogate endpoint for the duration of concern...

INTRODUCTION: To enhance the value of care, interventions should aim at improving endpoints that matter to patients. The preferences of head and neck cancer patients regarding treatment outcomes are therefore a major topic for patient-centered research. METHODS: A systematic review (PROSPERO number CRD42016035692) was conducted by searching electronic databases (Medline, Embase, Cochrane, CINAHL) for articles evaluating patient or surrogate preferences in head and neck cancer...

Purpose: To evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). Materials and Methods: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R2)...

Prospective, controlled clinical trials in postmenopausal osteoporosis typically compare effects of an active drug with placebo in addition to vitamin D and calcium supplementation in both treatment arms. While clinical benefits are documented, the effect of this supplementation in the placebo arm and in clinical practice on bone material composition properties is unknown. The purpose of the present study was to evaluate these bone quality indices (specifically mineral/matrix, nanoporosity, glycosaminoglycan content, mineral maturity/crystallinity, and pyridinoline content) in patients that either received long-term vitamin D (400-1200IU) and calcium (1...

For in situ remediation of groundwater contaminated by halogenated hydrocarbons Carbo-Iron(®), a composite of microscale activated carbon and nano Fe(0), was developed. Against the background of intended release of Carbo-Iron into the environment in concentrations in the g/L-range, potential ecotoxicological consequences were evaluated in the present study. The nano Fei(0) in Carbo-Iron acts as reducing agent and is oxidized in aqueous systems by chlorinated solvents, groundwater constituents (e.g. dissolved oxygen) and anaerobic corrosion...

BACKGROUND: The adequate suppression of nociception is, besides induction of unconsciousness and immobility, the main objective during anaesthesia. Analgesics, most commonly opioids, are usually titrated by established clinical surrogates of nociception. Recently, monitoring techniques became available to evaluate analgesia/nociception during anaesthesia and provide better measures then clinical evaluation alone. They are primarily derived from autonomic response on physiologic standard measures...

BACKGROUND: In acute decompensated heart failure (ADHF) with preserved ejection fraction (HFpEF) there are no surrogate endpoints for early phase trials. The aim of the current study was to evaluate whether a reduction in natriuretic peptides (NP) between acute hospital presentation to stable follow-up is associated with improved mortality and morbidity. METHODS: Patients presenting acutely to the hospital for ADHF with HFpEF enrolled in the Karolinska Rennes (KaRen) study and reporting N-terminal pro-B-type NP or B-type NP assessment at baseline hospital presentation and at 4-8weeks follow-up were prospectively studied...

OBJECTIVE: The purpose of this article is to examine the role of different imaging biomarkers, focusing in particular on the use of updated CT and PET response criteria for the assessment of oncologic treatment effectiveness in patients with lymphoma but also discussing other potential functional imaging methods and their limitations. CONCLUSION: Lymph nodes are commonly involved by metastatic solid tumors as well as by lymphoma. Evolving changes in cancer therapy for lymphoma and metastases have led to improved clinical outcomes...

BACKGROUND: Previous reviews have evaluated economic analyses of lipid-lowering therapies using lipid levels as surrogate markers for cardiovascular disease. However, drug approval and health technology assessment agencies have stressed that surrogates should only be used in the absence of clinical endpoints. OBJECTIVE: The aim of this systematic review was to identify and summarise the methodologies, weaknesses and strengths of economic models based on atherosclerotic cardiovascular disease event rates...

OBJECTIVE: Psoas muscle area (PMA) is a validated surrogate for muscle mass that can be easily measured from a clinical CT scan. This study sought to determine whether PMA was associated with post-operative mortality after endovascular or open aortic aneurysm repair. METHODS: A retrospective review was undertaken of patients who underwent elective endovascular or open aortic aneurysm repair between 2010 and 2015 at a tertiary vascular center in Montreal, Quebec, Canada...

: Hepatitis delta virus (HDV) is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG-IFNα) is effective in only 25%-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow-up, 5...

Objective: To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes. Methods: Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of Military Medical Science Academy of the PLA were enrolled.The clinical and pathological characteristics of patients were collected. The primary endpoint was pCR rate and the secondary endpoint was disease free survival (DFS)...

PURPOSE: Degarelix, a new GnRH receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over LHRH analogues in terms of avoiding "testosterone flare" and lower FSH levels. We set out to determine if pre-operative degarelix influenced surrogates of disease control in a randomized phase II study. EXPERIMENTAL DESIGN: 39 patients were randomly assigned to one of 3 different neo-adjuvant arms: degarelix only, degarelix/bicalutmaide, or LHRH agonist/bicalutamide...

Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock patients with admission blood lactate measurements in the prospective, observational, multicenter FINNAKI study. Repetitive lactate measurements were available in 496 patients for analyses of change in lactate values during ICU stay...

AIMS: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear. METHODS AND RESULTS: This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months...